The invention relates to methods of optimizing the therapeutic dose of a radiopharmaceutical to be given to a patient for treatment of a disease.
Radiopharmaceuticals are becoming more widely used for the treatment of disease in patients. Research continues, however, to elucidate the specifics of how to most effectively utilize radiopharmaceuticals in therapy. For example, the optimally effective administered activity of the radiopharmaceutical for any given radiopharmaceutical is not immediately evident. There is a substantial variance among patients in how long radiopharmaceuticals are retained in the body, so that a patient who retains a given radiopharmaceutical for a long time will get a much higher radiation dose than a similar-sized patient who retains the given radiopharmaceutical for a shorter period of time. This is not predictable from patient weight or body surface area alone. With varying clearance rates of any given radiopharmaceutical, differing radiation doses would be delivered to each patient per millicurie of the radiopharmaceutical administered, even if the patients have identical masses or body surface areas.
When conventional methods of dosing are used, e.g., simply based on the patient's size, there is the potential for causing adverse effects, on the one hand, and failing to provide an effective dose, on the other hand. Overdosing with the radiopharmaceutical may have dire consequences including damage to normal tissues, myeloablation, and death. Myeloablation typically necessitates hematopoietic stem cell reintroduction (usually a bone marrow transplant) in order for the patient to recover hematopoietic function. This is often an undesirable further procedure, especially in the treatment of seriously ill patients. Underdosing of the radiopharmaceutical is also not desired. If a standard dose below the known toxicity level for the particular radiopharmaceutical is given to each patient, then some patients may get enough radioactivity for treatment of the disease, but many others will not get enough. Repeat dosing is not a practicable alternative because of cost, resource, and patient general health considerations. Furthermore, it is extremely difficult to predict whether a certain patient in whom little or no effect has been seen with the standard therapy dose should be given a repeat dose, since the poor results may be due to some other physiological factors. If a repeat therapy dose is desired, it is difficult to ascertain how long after the initial dose the repeat dose should be administered and whether the repeat dose should be at full strength or a fraction of the initial dose.
Thus, it is highly desirable to adjust for these variabilities on an individual patient basis. Patient-specific dosimetry that takes into account the individual patient's pharmacokinetics and the radiation energy absorbed within the whole body of the patient is needed to determine the most appropriate dose for the individual patient.